Fasted Bioavailability Study of Cilostazol Tablets, 50mg: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fasted Bioavailability Study of Cilostazol Tablets, 50mg (NCT00685802), a randomized phase 1 study. The primary outcome is Maximum Plasma Concentration (Cmax).

2. Clinical Question

The primary outcome was the mean Cmax, measured in ng/mL. For the test tablets, the posted mean was 565.5; for Pletal®, it was 570.6. The posted mean difference was 5.08, with a confidence interval from -80.09 to 90.25. These summaries describe the observed peak concentrations and the uncertainty around the unadjusted difference. They do not, by themselves, establish that the formulations are equivalent or interchangeable. The registry record does not report the equivalence criteria, if any, used in the study’s original analysis.

3. Trial Design

This was a Phase 1, randomized, unmasked crossover study, listed as completed. The registry gives enrollment as 32. The study compared two drug interventions: cilostazol 50 mg tablets and Pletal® 50 mg tablets. Each intervention description specifies a single dose of 2 x 50 mg tablets after an overnight fast of at least 10 hours. The registry identifies the sponsor as Mutual Pharmaceutical Company, Inc.

In a crossover study, participants receive more than one intervention according to an assigned order, so comparisons can be made within participants. That is a general description of the design; the registry record does not report the treatment sequences, the number of periods, or the washout interval. It also does not say how randomization was generated or concealed. Masking is listed as none, meaning the study was not described as blinded.

The study began in 2004-06, reached primary completion in 2004-07, and is marked completed. Those dates describe the registry timeline, not the duration of participation for each person. The record does not report individual follow-up duration or the timing of each treatment period.

The primary outcome is maximum plasma concentration, or Cmax, for cilostazol. Blood samples were scheduled before dosing and at the listed post-dose time points through 48 hours. The outcome summary reports a mean and standard deviation for each treatment. It lists 29 observations for each treatment outcome, while the enrollment count is 32. The record does not explain the difference between those counts, so it cannot be attributed to withdrawal, missing measurements, or an analysis-population rule.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

First Intervention

Washout Period of 7 Days

Reasons for not completing this period:

Second Intervention

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Plasma Concentration (Cmax), measured over serial pharmacokinetic plasma concentrations were drawn prior to dose administration (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours after drug administration..

Cmax is the highest concentration of a drug measured in plasma after administration. In this study, it was used to describe the peak concentration reached by cilostazol after each formulation was taken under fasting conditions. The record defines the endpoint as the maximum or peak concentration that the test and reference products reach in plasma, and reports it in ng/mL.

To identify a peak, plasma concentrations are sampled at multiple times rather than measured only once. The registry lists a pre-dose sample at 0 hour and post-dose samples at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 16, 24, 36 and 48 hours. These scheduled measurements form the basis for identifying the maximum observed concentration. The record does not describe the calculation method used to derive Cmax from those measurements or how measurements outside the scheduled times were handled.

As a pharmacokinetic measure, Cmax addresses peak exposure. It is distinct from measures that describe total exposure over time, and a comparison of Cmax alone does not describe every aspect of bioavailability. The record lists three outcome measures in total, but only the primary Cmax result is detailed in the posted results. The other outcome measures are not reported in the registry record.

7. Results Posted in the Registry

• Pletal® 50 mg Tablets: mean 570.60 versus 565.52 on control; difference 5.08 (95% CI -80.09 to 90.25), standardized effect d = 0.03; z-test p = 0.907.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports continuous Cmax measurements summarized by a mean and standard deviation for each treatment. The posted comparison is a mean difference, with an estimate of 5.08 and a confidence interval from -80.09 to 90.25. The comparison is presented as an unadjusted recalculation from the posted summary statistics, rather than as a reported sponsor model. The original analysis method is not reported in the registry record.

What does a mean difference represent?

In general, a mean difference expresses the distance between two group means on the original measurement scale. Here, the reported means are 565.5 ng/mL for the test tablets and 570.6 ng/mL for Pletal®, and the posted comparison gives a difference of 5.08. The comparison labels Pletal® as the treatment being compared with the control treatment. A positive estimate therefore corresponds to a higher mean for Pletal® under that stated contrast. The difference is an estimate from the observed data, not a guarantee of the difference in a wider population.

Means are useful for describing the central level of a continuous outcome. They can, however, be affected by unusually high or low observations. The registry does not report distributions, medians, individual values, or diagnostic checks, so the shape of the Cmax data cannot be assessed from the posted summaries alone.

What do standard deviations and standard errors describe?

General distinction: a standard deviation describes how dispersed individual observations are around a mean. The posted standard deviations are 155.7 for the test tablets and 174.7 for Pletal®. A standard error describes uncertainty in an estimated mean. The registry lists standard errors of 28.91 and 32.44, respectively. These quantities answer different questions: observed variability is not the same as precision of the estimated mean.

The record reports 29 observations for each treatment outcome. It does not explain whether those are complete paired measurements, how many participants contributed to both treatments, or how missing observations were handled. That information is especially relevant in a crossover design, where the same participant may contribute measurements under both treatments. A paired analysis can use within-participant information, while a comparison that treats observations as independent may not reflect that structure. The registry record does not identify which approach was used in the original analysis.

How should the p-value be understood?

The posted unadjusted p-value is 0.907. In general, a p-value is calculated under a null hypothesis and a specified statistical model; it measures how unusual the observed result, or a more extreme result, would be if that model and null hypothesis held. It is not the probability that the null hypothesis is true. The registry does not report the test statistic, the null hypothesis details, or the model used for this p-value, so its precise analysis context is not reported in the registry record.

The planning assumptions list a two-sided significance level of 0.05, but those assumptions apply to the planning illustration, not necessarily to the trial’s original analysis. The original significance threshold and analysis plan are not reported in the registry record. The p-value does not substitute for an equivalence test: such a conclusion requires a defined equivalence margin and an appropriate analysis, neither of which is reported.

Why does the crossover structure matter?

General explanation: crossover studies can compare treatments within the same participants. Because each participant can serve as their own comparison, participant-level characteristics that do not change between treatment periods may be accounted for through paired analysis. This advantage depends on a suitable design and analysis. Treatment order, period effects, carryover, and within-participant correlation can matter. The registry identifies the model as crossover but does not report sequence details, washout, period effects, or a model addressing these features. It is therefore not possible to tell from the record how the original analysis handled them.

The posted recalculation uses summary statistics and is explicitly unadjusted. It should be distinguished from a crossover model that could use paired participant-level data. The record does not provide individual observations or the within-participant covariance needed to reconstruct such a model from the summaries. No additional adjusted estimate should be inferred from the posted means and standard deviations.

What is the role of the confidence interval?

General explanation: a confidence interval gives a range of values compatible with the data and the method used to construct the interval. Narrower intervals indicate greater precision, while wider intervals indicate less precision. The posted interval for the mean difference runs from -80.09 to 90.25. The confidence level and construction method are not reported in the registry record. Because the interval includes negative and positive values, the posted estimate is compatible with differences in either direction under the interval’s method. It does not define an equivalence range.

These methods explanations distinguish what the summaries show from what cannot be recovered from them. The record provides descriptive statistics, an unadjusted comparison, and planning illustrations. It does not provide the full statistical analysis plan, the original model, or participant-level data.

10. Confidence Intervals and Precision

The mean Cmax estimates are 565.5 ng/mL for cilostazol 50 mg tablets and 570.6 ng/mL for Pletal® 50 mg tablets. The posted mean difference is 5.08, with a confidence interval from -80.09 to 90.25. The interval is much wider than the point estimate and spans values below and above zero. Thus, the point estimate alone gives an incomplete picture of the uncertainty in the comparison.

In general, a confidence interval represents a range of effect values compatible with the observed data and the method used to calculate the interval. Its width conveys precision: a wider range leaves more uncertainty about the size and direction of the underlying difference. The confidence level and interval-construction method are not reported in the registry record, so these cannot be used to judge the interval’s calibration or reproduce it.

The interval’s inclusion of zero does not prove that there is no difference. Nor does it demonstrate equivalence. Equivalence requires a prespecified range of differences considered acceptably small and an analysis showing that uncertainty falls within that range. An equivalence margin is not reported in the registry record.

The outcome summaries give 29 observations for each treatment, while enrollment was 32. The record does not explain the analysis population, the availability of paired observations, or the handling of missing data. Those details affect how precisely the comparison can be interpreted. The posted interval is therefore the available summary of uncertainty, but its underlying analysis cannot be fully assessed from the registry record.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning estimates are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The original trial’s design assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the estimates are 16,656 participants per arm for 80% power and 22,297 participants per arm for 90% power. At 75% of the observed effect, the corresponding estimates are 29,609 and 39,638 participants per arm. At 50% of the observed effect, they are 66,621 and 89,186 participants per arm.

In plain language, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting an effect of the specified size if that effect were the true one. The 90% column describes the analogous chance at 90% power. These are planning probabilities, not guarantees for a particular study. Smaller effects require more participants to detect under otherwise unchanged assumptions. The very large estimates reflect the small observed mean difference used as the planning basis; they should not be read as evidence that such a study was planned or conducted. This is not observed power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 5.080; pooled standard deviation σ = 165.469.
2. n = 2 × (1.96 + 0.842)² × 165.469² / 5.080² = 16,655.0, rounded up to 16,656 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 5.08000000000004                      # observed difference in means
sigma <- 165.469373752365                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(685802)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 16,656 (80% power), 22,297 (90% power)
 75% of observed effect: n per arm = 29,609 (80% power), 39,638 (90% power)
 50% of observed effect: n per arm = 66,621 (80% power), 89,186 (90% power)
power.t.test: 16656 
Simulated power at n = 16,656 per arm: 0.803 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, but only the primary Cmax outcome is described in the posted results. No secondary outcomes are posted. The record does not report whether multiple outcomes, multiple time points, or multiple statistical comparisons were included in the original analysis, or whether any adjustment for multiplicity was planned or applied.

In general, testing multiple hypotheses can increase the chance of obtaining at least one apparently unusual result by chance. Statistical plans may address this by defining a primary endpoint, ordering analyses, or adjusting interpretation across tests. The registry identifies Cmax as primary, but it does not provide a complete testing hierarchy or multiplicity procedure. The posted p-value is unadjusted, so it should not be described as adjusted for multiple comparisons.

The registry reports no analyses in its analysis listing. It also does not report the statistical analysis population, criteria for inclusion, or a participant flow explaining the enrollment of 32 and 29 observations per treatment outcome. The adverse event groups list 31 and 30 participants at risk, but the record does not explain how those safety populations relate to the outcome populations. The reason for these different counts is not reported in the registry record.

Missing-data methods are not reported in the registry record. There is no description of whether missing concentration measurements occurred, how they were handled, or whether any sensitivity analyses were conducted. In general, the impact of missing data depends on how much is missing and why; without those details, the potential influence on the reported estimate cannot be assessed.

The original statistical plan, analysis model, handling of crossover sequence and period, and any interim analyses are not reported in the registry record. No interim-analysis procedure should be inferred. These gaps limit evaluation of whether the posted comparison follows the study’s original prespecified approach and whether the result is robust to alternative analytic choices.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3.22% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists zero serious adverse events among 31 participants at risk for cilostazol 50 mg tablets and zero among 30 participants at risk for Pletal® 50 mg tablets. No serious adverse-event terms are listed. These counts describe the safety figures posted for the study; they do not establish that serious events could not occur, particularly because the record does not provide additional detail on observation duration or event ascertainment.

The registry also lists 10 participants with other adverse events in the cilostazol 50 mg tablet group and 12 in the Pletal® 50 mg tablet group, with 31 and 30 participants at risk, respectively. These are distinct from the serious-event counts. The record does not provide the specific non-serious event terms in the registry record for this comparison, so their types and severity cannot be described.

Deaths are not reported in the registry record. The differing at-risk counts and their relationship to the enrolled population are also not explained. These safety figures should be read as posted counts, not as a complete assessment of comparative safety or as evidence about risks beyond the study population and follow-up recorded.

15. What the Result Does, and Does Not, Mean

The posted results describe Cmax after single fasted doses of the test cilostazol tablets and Pletal®. The mean values were 565.5 ng/mL and 570.6 ng/mL, respectively. The estimated mean difference was 5.08, and the confidence interval extended from -80.09 to 90.25. The unadjusted p-value was 0.907. Taken together, these statistics describe a small point estimate alongside uncertainty that includes differences in either direction.

They do not establish that the formulations are equivalent. Equivalence is a specific statistical claim requiring a prespecified margin and a suitable analysis; the margin and original analysis are not reported in the registry record. The results also do not establish that the products differ. A high p-value is not proof of equality, and a confidence interval that includes zero is not proof that the true difference is zero.

The outcome concerns peak plasma concentration after a single dose under fasting conditions. It does not, by itself, describe total exposure, repeated dosing, clinical outcomes, or use under other conditions. The study population is described in the registry as healthy, and the record does not provide detailed participant characteristics. The findings therefore have a limited scope defined by the study setting and the posted endpoint.

The available summaries also leave important analytic details unresolved. The registry does not report the crossover analysis model, participant-level paired data, missing-data handling, or analysis population. The outcome count of 29 per treatment is smaller than the enrollment of 32, and the reasons are not reported in the registry record. Those limitations constrain assessment of both the estimate and its precision.

The appropriate interpretation is descriptive: the reported mean Cmax values were close, while the interval around their difference was broad. The registry record does not support a definitive claim of equivalence, absence of a difference, or clinical effect.

16. Why This Trial Matters Statistically

This study illustrates why a point estimate and its uncertainty need to be read together. The means, 565.5 ng/mL and 570.6 ng/mL, are close, and the estimated difference is 5.08. Yet the confidence interval ranges from -80.09 to 90.25. The estimate alone may appear decisive, but the interval shows that the comparison is imprecise relative to the point estimate.

It also demonstrates the distinction between a non-significant result and evidence of equivalence. The unadjusted p-value is 0.907, but a p-value does not establish that two formulations are equivalent. A formal equivalence conclusion depends on a prespecified margin and an analysis designed to evaluate that margin. Neither is reported in the registry record. Statistical interpretation must therefore stay within the scope of the posted comparison.

The crossover design raises a further methodological issue. General principle: within-participant comparisons can use information about how each participant responds to both treatments. That requires the paired structure to be represented in the analysis. The registry labels the study crossover, but the posted comparison is an unadjusted recalculation from summary statistics, and the original model is not reported. Without participant-level data or model details, the influence of pairing cannot be evaluated.

Finally, the planning illustrations show how sample-size requirements depend on the assumed effect size. The estimates increase as the planned effect becomes a smaller fraction of the observed effect. They are planning scenarios under stated assumptions, not a description of the original design or evidence about the trial’s power. Together, these features make the study useful for understanding the interpretation of pharmacokinetic summaries, confidence intervals, crossover analysis, and planning estimates.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record gives limited detail about the crossover design. It does not report treatment sequences, the number of periods, washout duration, or procedures for managing possible period or carryover effects. Those details are relevant to evaluating whether the comparison appropriately reflects the design.

The posted outcome summaries list 29 observations for each treatment, while enrollment is 32. The record does not explain the discrepancy or identify the analysis population. It does not say whether each participant contributed a measurement under both treatments, whether any measurements were missing, or how incomplete records were handled. This limits assessment of the unadjusted comparison and its uncertainty.

The original statistical analysis plan and model are not reported in the registry record. The posted comparison is an unadjusted recalculation from summary statistics, which cannot account for the crossover structure using participant-level pairing. The record also does not report the confidence level or construction method for the interval, or an equivalence margin. These omissions prevent a formal assessment of equivalence.

Only the primary Cmax result is detailed, although three outcome measures are listed. The other outcome measures and any secondary analyses are not reported in the registry record. Multiplicity procedures and interim analyses are also not reported. The record does not provide detailed participant characteristics beyond the listed healthy condition, or enough safety follow-up information to interpret the event counts beyond their posted totals.

The study assessed peak concentration after a single dose under fasting conditions. Its posted endpoint does not describe other pharmacokinetic measures or outcomes outside that setting. These design and reporting limits should be kept in view when interpreting the result.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Fasted Bioavailability Study of Cilostazol Tablets, 50mg — NCT00685802.
• Registry record last updated 2009-12-22; status last verified 2009-11.
• Results first posted 2009-12-22.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

NCT00685802 is a completed Phase 1 randomized, unmasked crossover study of cilostazol 50 mg tablets and Pletal® 50 mg tablets under fasting conditions. The registry lists enrollment of 32 and describes a single dose of 2 x 50 mg tablets after an overnight fast of at least 10 hours for each intervention.

The primary outcome was mean maximum plasma concentration (Cmax), measured in ng/mL. The reported means were 565.5 for the test tablets and 570.6 for Pletal®. The posted mean difference was 5.08, with a confidence interval from -80.09 to 90.25 and an unadjusted p-value of 0.907. The result is descriptive and does not establish equivalence.

The record does not report the original analysis model, equivalence margin, analysis populations, or reasons for the difference between enrollment and the outcome counts. It lists zero serious adverse events in each group’s at-risk population and does not report deaths.